P1293: LOW-DOSE POST-TRANSPLANT CYCLOPHOSPHAMIDE WITH G-CSF/ATG BASED HAPLOIDENTICAL PROTOCOL PROVIDES FAVORABLE DECREASE IN ACUTE GRAFT-VERSUS-HOST DISEASE FOR SAA PATIENTS
Authors: MA Xiao-DI, Zhengli Xu, Tingting Han, Yuan-Yuan Zhang, Wei Han, Haixia Fu, Xiao-Hui Zhang, Fan Lin, Xiao-Jun Huang, Lanping Xu
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Patients suffering from severe acquired aplastic anemia (SAA) are at a high risk of death without prompt and appropriate treatment. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has drawn increasing interest as a curative option for SAA. However, graft failure (GF) and severe graft-versus-host disease (GvHD) are two primary obstacles to successful haplo-HSCT. Over decades, G-CSF/ antithymocyte globulin (ATG)-based protocol (the Beijing Protocol) has achieved favorable engraftment and survival outcomes both as an upfront and salvage treatment in SAA patients, whereas the incidence of GvHD is relatively high. Apart from the Beijing Protocol, high-dose post-transplant cyclophosphamide (HD-PTCy, the Baltimore regimen) has been successfully used in haplo-HSCT for SAA, and an inspiring decrease in aGVHD albeit with somewhat high rates of GF has been consecutively reported. Therefore, it is reasonable to modify the current two transplant protocols to exploit their strength and avoid unfavorable conditions. Aims: In this study, we modified the conventional Beijing Protocol: retaining the standard dose of ATG from Beijing protocol to provide sufficient immunosuppression; dividing the full-dose Cy (200 mg/kg in total) was divided into 42.75 mg/kg Cy on day -5 to day -2 and LD-PTCy (14.5 mg/kg on days +3 and +4/+5), hoping to reduce the incidence of severe aGVHD and to guarantee successful and stable engraftment. Methods: Between August 2020 and August 2022, 17 patients diagnosed with SAA accepting haplo-HSCT under the PTCy regimen at Peking University People’s Hospital were enrolled in this study. Here we reported the clinical outcomes of 17 patients who received this modified protocol. Results: Seven patients were males (41.18%) and the median age of these patients was 12 (range, 5-39) years old. The median follow-up was 522 days (range, 138-859 days). No patient developed primary graft failure. All patients achieved neutrophil and platelet engraftment at median times of 12 days (range, 11–20 days) and14 days (range, 8-36 days). During our follow-up, no patients developed grade Ⅲ-Ⅳ aGvHD. The cumulative incidence of grade ⅡaGvHD at 100 days was 23.5% (95% CI, 1.0%-46.0%). Four patients (23.5%) developed chronic GvHD of skin or eyes and all of which were mild. All patients are alive by the end of the follow-up, with a failure-free survival rate of 100%. Four (23.5%) patients developed grade Ⅱ bladder toxicity, two (11.8%) patients developed grade Ⅱ cardiotoxicity. The rate of cytomegalovirus (CMV) reactivation was 82.4% (95% CI, 64.3%-100%). The rate of Epstein-Barr virus (EBV) reactivation was 16.7% (95% CI, 0%-35.7%). No CMV disease and post-transplantation lymphoproliferative disorder (PTLD) occurred among these patients. Summary/Conclusion: In conclusion, our data revealed that it is feasible and effective to use the G-CSF/ATG/LD-PTCy protocol in haplo-HSCT for SAA. With RIC preparative regimen and the use of LD-PTCy, the incidence of severe GVHD was reduced and successful and stable engraftment was achieved.Figure 1 Keywords: Acute graft-versus-host disease, Cyclophosphamide, Aplastic anemia, Haploidentical stem cell transplantation